IP Library › Granted Patent US 12,582,674
Granted Patent B2
US 12,582,674 · App. 18/152,140 · Granted Mar 24, 2026

Methods and treatment of trauma

Inventors: Andrew Dunham (Tower Lakes, IL); Tatsuro Yoshida (West Newton, MA)
Assignee: Hemanext Inc.
A61K35/14A61P7/04
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Quick Facts
Patent No.
US 12,582,674
App. No.
18/152,140
Granted
Mar 24, 2026
Kind
B2
Abstract

Methods for the reversal of hemorrhagic shock or hemorrhagic trauma. Methods for reducing levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in a trauma patient through the administration of stored oxygen reduced blood products.

Claims (20)

1 . A method for reducing levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in a trauma patient in need thereof comprising administering stored oxygen reduced blood to the trauma patient in need thereof, the stored oxygen reduced blood comprising a blood product having a reduced oxygen saturation level prior to and during storage, wherein the trauma patient in need thereof has liver injury or liver damage, wherein the trauma patient in need thereof has elevated levels of AST and ALT prior to the administering, and wherein the levels of AST and ALT are each reduced independently by at least 5% in the trauma patient in need thereof after the administering as compared to a trauma patient administered non-oxygen reduced blood stored under conventional conditions.

2 . The method of claim 1 , wherein the trauma patient in need thereof is a hemorrhagic trauma patient.

3 . The method of claim 2 , wherein the hemorrhagic trauma patient has a trauma selected from the group consisting of surgery, a penetrating wound, blunt force trauma, injury due to a fall, and injury due to a car accident.

4 . The method of claim 1 , wherein the stored oxygen reduced blood has an oxygen saturation (SO 2 ) level of 20% or less prior to and during storage.

5 . The method of claim 1 , wherein the stored oxygen reduced blood is stored for a period of up to 28 days prior to the administering.

6 . The method of claim 1 , wherein the stored oxygen reduced blood is stored for a period of up to 42 days prior to the administering.

7 . The method of claim 1 , wherein the stored oxygen reduced blood is stored oxygen and carbon dioxide reduced blood.

8 . The method of claim 7 , wherein the stored oxygen and carbon dioxide reduced blood has an oxygen saturation (SO 2 ) level of 20% or less and a partial pressure of CO 2 (pCO 2 ) of between 10 and 30 millimeters of mercury (mmHg) prior to and during storage.

9 . The method of claim 1 , wherein the levels of AST and ALT are each reduced independently by at least 20% in the trauma patient in need thereof after the administering as compared to a trauma patient administered non-oxygen reduced blood stored under conventional conditions.

10 . The method of claim 9 , wherein the levels of AST and ALT are each reduced independently by at least 50% in the trauma patient in need thereof after the administering as compared to a trauma patient administered non-oxygen reduced blood stored under conventional conditions.

11 . The method of claim 1 , wherein the level of AST is reduced by at least 20% and the level of ALT is reduced by at least 50% in the trauma patient in need thereof after the administering as compared to a trauma patient administered non-oxygen reduced blood stored under conventional conditions.

12 . The method of claim 1 , wherein the level of AST is reduced by at least 50% and the level of ALT is reduced by at least 20% in the trauma patient in need thereof after the administering as compared to a trauma patient administered non-oxygen reduced blood stored under conventional conditions.

13 . The method of claim 1 , wherein the trauma patient in need thereof has one or more preexisting or underlying conditions selected from the group consisting of diabetes, ischemic heart disease, systemic inflammatory syndrome brought on by trauma or infection, multiple organ failure brought on by trauma or infection, smoke inhalation, chronic pulmonary obstructive disease such as systemic inflammation due to infection, a coagulopathy disorder, and an autoimmune disease.

14 . The method of claim 13 , wherein the trauma patient has two of the preexisting or underlying conditions.

15 . The method of claim 1 , wherein the stored oxygen reduced blood comprises an anticoagulant.

16 . The method of claim 1 , wherein the stored oxygen reduced blood comprises an additive solution.

17 . The method of claim 16 , wherein the additive solution is selected from the group consisting of additive solution 1 (AS-1), additive solution 3 (AS-3), additive solution 5 (AS-5), saline-adenine-glucose-mannitol (SAGM), phosphate-adenine-glucose-guanosine-saline-mannitol (PAGG-SM), phosphate-adenine-glucose-guanosine-gluconate-mannitol (PAGG-GM), mannitol-adenine-phosphate (MAP), additive solution 7 (AS-7), erythrosol-5 (ESOL-5), experimental additive solution 61 (EAS61), oxygen free additive solution 1 (OFAS1), oxygen free additive solution 3 (OFAS3), and any combination thereof.

18 . The method of claim 1 , wherein the blood product having a reduced oxygen saturation level is selected from the group consisting of oxygen reduced whole blood, oxygen reduced leukoreduced red blood cells, oxygen reduced and platelet reduced red blood cells, oxygen- and platelet-reduced leukoreduced red blood cells, oxygen reduced packed red blood cells, oxygen reduced platelet reduced packed red blood cells, oxygen reduced leukoreduced packed red blood cells, and oxygen- and platelet-reduced, leukoreduced packed red blood cells.

19 . The method of claim 1 , wherein the stored oxygen reduced blood has an oxygen saturation (SO 2 ) level of 10% or less prior to and during storage.

20 . The method of claim 1 , wherein the stored oxygen reduced blood has an oxygen saturation (SO 2 ) level of 5% or less prior to and during storage.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 11, 2023
From: DUNHAM, ANDREW; YOSHIDA, TATSURO
To: NEW HEALTH SCIENCES, INC.
Reel/Frame 062346/0659 →
CHANGE OF NAME Recorded Jan 11, 2023
From: NEW HEALTH SCIENCES, INC.
To: HEMANEXT INC.
Reel/Frame 063825/0302 →
Continuity (8)
Continuation 17339283 · Jun 4, 2021
Continuation 16994243 · Aug 14, 2020
Continuation 16903108 · Jun 16, 2020
Continuation 16849614 · Apr 15, 2020
Continuation 16791697 · Feb 14, 2020
Continuation 16614683
Provisional Application 62508783 · May 19, 2017
Related Publication 20230165896A1 · Jun 1, 2023
References Cited (92)
US 4769318A · Hamasaki et al. · 1988 [cited by applicant]
US 4880786A · Sasakawa et al. · 1989 [cited by applicant]
US 5476764A · Birensky · 1995 [cited by applicant]
US 5624794A · Bitensky et al. · 1997 [cited by applicant]
US 5789151A · Bitensky et al. · 1998 [cited by applicant]
US 6162396A · Bitensky et al. · 2000 [cited by applicant]
US 6413713B1 · Serebrennikov · 2002 [cited by applicant]
US 6447987B1 · Hess et al. · 2002 [cited by applicant]
US 9968718B2 · Yoshida et al. · 2018 [cited by applicant]
US 10335538B2 · Balakrishnan · 2019 [cited by applicant]
US 10583192B2 · Sowemimo-Coker · 2020 [cited by applicant]
US 10898517B2 · Dunham · 2021 [cited by examiner]
US 10898718B2 · Srivastava et al. · 2021 [cited by applicant]
US 11026970B2 · Dunham et al. · 2021 [cited by applicant]
US 11026971B2 · Dunham et al. · 2021 [cited by applicant]
US 11033581B2 · Dunham et al. · 2021 [cited by applicant]
US 11052110B2 · Dunham et al. · 2021 [cited by applicant]
US 20100311657A1 · Abuchowski · 2010 [cited by applicant]
US 20160045650A1 · Yoshida et al. · 2016 [cited by applicant]
US 20180133255A1 · Yoshida · 2018 [cited by applicant]
US 20180338488A1 · Wolf · 2018 [cited by applicant]
US 20190167792A1 · Sowemimo-Coker · 2019 [cited by applicant]
US 20190388467A1 · D'Alessandro · 2019 [cited by applicant]
US 20200179446A1 · Dunham · 2020 [cited by applicant]
US 20200197438A1 · Dunham · 2020 [cited by applicant]
US 20200237818A1 · Dunham · 2020 [cited by applicant]
US 20200276234A1 · D'Alessandro · 2020 [cited by applicant]
CN 103732056A · 2014 [cited by applicant]
JP 2014518283 · 2014 [cited by applicant]
WO WO2008100140A1 · 2008 [cited by applicant]
WO WO2013006631A1 · 2013 [cited by applicant]
WO WO2016187353A1 · 2016 [cited by applicant]
WO WO2017223377A1 · 2017 [cited by applicant]
Brown., “Length of red cell unit storage and risk for delirium after cardiac surgery,” [cited by applicant]
Chaplin et al., “The Proper Use of Previously Frozen Red Blood Cells for Transfusion,” [cited by applicant]
Ciccia et al., “Pediatric acute kidney injury: prevalence, impact and management challenges,” [cited by applicant]
D'Alessandro et al., “Metabolomics of AS-5 RBCs supernatants following routine storage,” [cited by applicant]
D'Alessandro et al., “An update on red blood cell storage lesions, as gleaned through biochemistry and omics technologies,” [cited by applicant]
D'Alessandro et al., “Routine storage of red blood cell (RBC) units in additive solution-3: a comprehensive investigation of the RBC metabolome,” [cited by applicant]
D'Alessandro et al., “Red blood cell storage in additive solution-7 preserves energy and redox metabolism: a metabolomics approach,” [cited by applicant]
D'Alessandro et al., “Citrate metabolism in red blood cells stored in additive solution-3,” [cited by applicant]
D'Alessandro et al., “Omics markers of the red cell storage lesion and metabolic linkage,” [cited by applicant]
DeMers et al., “Physiology, Mean Arterial Pressure,” [cited by applicant]
Extended European Search Report dated Nov. 28, 2022 issued in European Appln. 22191477.3. [cited by applicant]
Flegel et al., “Does prolonged storage of red blood cells harm?” [cited by applicant]
Fox et al., “Earlier Endpoints are Required for Hemorrhagic Shock Trials Among Severely Injured Patients,” [cited by applicant]
Fukuma et al., “Prehospital lactate improves prediction of the need for immediate interventions for hemorrhage after trauma,” [cited by applicant]
Gowda et al., “Markers of renal function tests,” [cited by applicant]
Hashmi et al., “Predictors of mortality of geriatric trauma patients: a systematic review and meta-analysis,” [cited by applicant]
Hod et al., “Transfusion of human volunteers with older, stored red blood cells produces extravascular hemolysis and circulating non-transferrin-bound iron,” [cited by applicant]
Holcomb, “Optimal Use of Blood Products in Severely Injured Trauma Patients,” [cited by applicant]
Jy et al., “Microparticles in stored red blood cells as potential mediators of transfusion complications,” [cited by applicant]
Kim-Shapiro et al., “Storage lesion: role of red blood cell breakdown,” [cited by applicant]
Kreutziger et al., “Admission blood glucose predicted hemorrhagic shock in mortality in trauma patients,” [cited by applicant]
Laird et al., “Relationship of early hyperglycemia to mortality in trauma patients,” [cited by applicant]
Liu et al., “Mechanism of faster NO scavenging by stored red blood cells,” [cited by applicant]
Nall, “Understanding Mean Arterial Pressure,” [cited by applicant]
Norton et al., “Global Health Injuries,” [cited by applicant]
Prestia et al., “Transfusion of stored blood impairs host defenses against Gram-negative pathogens in mice,” [cited by applicant]
Redlin et al., “Red blood cell storage duration is associated with various clinical oucomes in pediatric cardiac surgery,” [cited by applicant]
Rogers et al., “Storage duration of red blood cell transfusion and Clostridium difficile infection: a within person comparison,” [cited by applicant]
Roback et al., “Insufficient nitric oxide bioavailability: a hypothesis to explain adverse effects of red blood cell transfusion,” [cited by applicant]
Roback et al., “Metabolomics of AS-1 RBCs Storage,” [cited by applicant]
Reynolds et al., “The transfusion problem: role of aberrant S-nitrosylation,” [cited by applicant]
Reisz et al., “Oxidative modifications of glyceraldehyde 3-phosphate dehydrogenase regulate metabolic reprogramming of stored red blood cells,” [cited by applicant]
Regnier et al., “Prognostic significance blood lactate and lactate clearance in trauma patients,” [cited by applicant]
Simti et al., “Red blood cell storage time and transfusion: current practice, concerns and future perspectives,” [cited by applicant]
Spinella et al., “Does the storage duration of blood products affect outcomes in critically ill patients,” [cited by applicant]
Spinella et al., “Properties of stored red blood cells: understanding immune and vascular reactivity,” [cited by applicant]
Treeprasertsuk et al., “Urine neutrophil gelatinase-associated lipoclin: a diagnostic and prognostic marker for acute kidney injury (AKI) in hospitalized cirrhotic patients with AKI-prone conditions,” [cited by applicant]
Valeri et al., “The survival, function, and hemolysis of human RBCs stored at 4 degrees C in additive solution (AS-a, AS-3, or AS-5) for 42 days and then biochemically modified, frozen, thawed, washed, and stored at 4 d… [cited by applicant]
Wang et al., “Transfusion of older stored blood worsens outcomes in canines depending on the presence of severity of pneumonia,” [cited by applicant]
Weinberg et al., “Red blood cell age and potentiation of transfusion-related pathology in trauma patients,” [cited by applicant]
Wither et al., “Hemoglobin oxidation at functional amino acid residues during routine storage of red blood cells,” [cited by applicant]
Yoshida et al., “Extended storage of red blood cells under anaerobic conditions,” [cited by applicant]
Yoshida et al., “The effects of additive solution pH and metabolic rejuvenation on anaerobic storage of red cells,” [cited by applicant]
Yoshida et al., “Reduction of microparticle generation during anaerobic storage of red blood cells,” [cited by applicant]
Zhang et al., “Lactate clearance is a useful biomarker for the prediction of all-cause mortality in critically ill patients: a systematic review and meta-analysis,” [cited by applicant]
Zimring, “Established and theoretical factors to consider in assessing the red cell storage lesion,” [cited by applicant]
Zhu et al., “Impaired adenosine-5′-triphosphate release from red blood cells promotes their adhesion to endothelial cells: a mechanism of hypoxemia after transfusion,” [cited by applicant]
Zhu et al., “Autologous Blood Transfusion Stimulates Wound Healing in Diabetic Mice,” [cited by applicant]
Extended European Search Report dated Jan. 24, 2025, issued in European Appln. 24207661.0. [cited by applicant]
Search Report dated Aug. 1, 2023 in Chinese Patent Application No. 201880032791.2 (in English). [cited by applicant]
Wang Heming, “Traumatic Shock Traditional Chinese Medicine Orthopedics,” China Press of Traditional Chinese Medicine the 1st Edition, pp. 111-112 (Mar. 2017) (Shanghai, China) (with translation). [cited by applicant]
Takeda, “Transfusion of Red Blood Cell Stored for More than One Week Prolongs Anaerobic Metabolism in Hemorrhagic Rats,” [cited by applicant]
Search Report dated Feb. 23, 2023, in Chinese Patent Application No. 201880032791.2 (with English translation). [cited by applicant]
U.S. Appl. No. 16/614,683, filed Nov. 18, 2019, which issued as U.S. Pat. No. 11,026,970 on Jun. 8, 2021. [cited by applicant]
U.S. Appl. No. 16/791,697, filed Feb. 14, 2020, which issued as U.S. Pat. No. 10,898,517 on Jan. 26, 2021. [cited by applicant]
U.S. Appl. No. 16/849,614, filed Apr. 15, 2020, which issued as U.S. Pat. No. 11,033,581 on Jun. 15, 2021. [cited by applicant]
U.S. Appl. No. 16/903,108, filed Jun. 16, 2020, which issued as U.S. Pat. No. 11,026,971 on Jun. 8, 2021. [cited by applicant]
U.S. Appl. No. 16/994,243, filed Aug. 14, 2020, which issued as U.S. Pat. No. 11,052,110 on Jul. 6, 2021. [cited by applicant]
U.S. Appl. No. 17/339,283, filed Jun. 4, 2021, which issued as U.S. Pat. No. 11,576,931 on Feb. 14, 2023. [cited by applicant]